Deciphering Immunosenescence From Child to Frailty: Transcriptional Changes, Inflammation Dynamics, and Adaptive Immune Alterations
Aging induces significant alterations in the immune system, with immunosenescence contributing to age-related diseases. Peripheral blood mononuclear cells (PBMCs) offer a convenient and comprehensive snapshot of the body's immune status. In this study, we performed an integrated analysis of PBMCs using both bulk-cell and single-cell RNA-seq data, spanning from children to frail elderlies, to investigate age-related changes. We observed dynamic changes in the PBMC transcriptome during healthy aging, including dramatic shifts in inflammation, myeloid cells, and lymphocyte features during early life, followed by relative stability in later stages. Conversely, frail elderly individuals exhibited notable disruptions in peripheral immune cells, including an increased senescent phenotype in monocytes with elevated inflammatory cytokine expression, heightened effector activation in regulatory T cells, and functional impairment of cytotoxic lymphocytes. Overall, this study provides valuable insights into the complex dynamics of immunosenescence, elucidating the mechanisms driving abnormal inflammation and immunosuppression in frailty.
Authors
- Hao Wang (ORCID: https://orcid.org/0000-0003-2169-1712)
- Oscar Junhong Luo (ORCID: https://orcid.org/0000-0002-1266-3069)
- Lipeng Mao (ORCID: https://orcid.org/0000-0002-0155-6700)
- Chanchan Xiao (ORCID: https://orcid.org/0000-0001-7135-9051)
- Qiuyue Feng (ORCID: https://orcid.org/0009-0008-8378-9145)
- Wenpu Lai (ORCID: https://orcid.org/0000-0002-7743-3950)
- Guobing Chen
- Yangqiu Li (ORCID: https://orcid.org/0000-0002-0974-4036)
- Juan Wang (ORCID: https://orcid.org/0000-0001-6027-1505)
- Zhenhua Li (ORCID: https://orcid.org/0000-0001-7297-1007)
- Yue Zhu (ORCID: https://orcid.org/0000-0002-3463-6037)
- Jiacheng He (ORCID: https://orcid.org/0009-0007-1016-4040)
- Lei Wen (ORCID: https://orcid.org/0000-0001-5128-8305)
- Yi Zhu (ORCID: https://orcid.org/0000-0002-5748-6940)
Institutions
- Jinan University (CN)
- Fifth Affiliated Hospital of Zhengzhou University (CN)
- First Affiliated Hospital of Jinan University (CN)
- University College London (GB)
Publication Details
- Journal
- Aging Cell
- Published
- 2025-04-26
- DOI
- https://doi.org/10.1111/acel.70082
- Citations
- 7
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Jinan University
- K. C. Wong Education Foundation
- Guangdong Provincial People's Hospital
- Guangdong Special Support Plan
- Basic and Applied Basic Research Foundation of Guangdong Province